Salinomycin (SAL), a polyether antibiotic exerting K⁺/H⁺-exchange on cellular membranes, effectively kills cancer stem cells. A series of cationic triphenylphosphonium (TPP⁺)-linked SAL derivatives were synthesized aiming to render them mitochondria-targeted. Remarkably, attaching a TPP⁺ moiety via a triazole linker at the C-20 position of SAL (compound 5) preserved the ion carrier potency of the antibiotic, while analogs with TPP⁺ linked at the C-1 position of SAL (6, 8) were ineffective. On planar bilayer lipid membranes (BLM), the SAL analogs 6 and 8 exhibited slow electrical current relaxation upon a voltage jump, similar to previously studied alkyl-TPP compounds. However, 5 demonstrated much faster current relaxation, which suggested its high permeability through BLM resulting in its pronounced potency to transport potassium and hydrogen ions across both artificial (liposomal) and mitochondrial membranes. SAL and 5 did not induce a steady-state electrical current through the planar lipid bilayer, thereby confirming that the transport mechanism is the electrically silent K⁺/H⁺ exchange. The ion exchange mediated by 5 in energized mitochondria was more active than that caused by SAL, which was apparently due to accumulation of 5 in mitochondria. Thus, compound 5 can be regarded as a promising lead compound for testing anticancer and antimicrobial activity.

盐霉素 ( SAL ) 是一种聚醚抗生素，可在细胞膜上进行K ⁺ /H ^{+交换，可有效杀死癌症干细胞。}合成了一系列阳离子三苯基鏻 (TPP ⁺ )-连接的SAL衍生物，旨在使其靶向线粒体。值得注意的是，通过三唑接头在SAL（化合物5 ）的 C-20 位置连接 TPP ⁺部分保留了抗生素的离子载体效力，而具有 TPP ⁺的类似物连接在SAL的C- 1位置（6、8) 无效。在平面双层脂质膜 (BLM) 上，SAL类似物6和8在电压跳跃时表现出缓慢的电流弛豫，类似于先前研究的烷基-TPP 化合物。然而，5表现出更快的电流弛豫，这表明其通过 BLM 的高渗透性导致其在人工（脂质体）和线粒体膜上转运钾和氢离子的显着效力。SAL和5没有通过平面脂质双层诱导稳态电流，从而证实了传输机制是电沉默的 K ⁺ /H ⁺交换。通电线粒体中5介导的离子交换比SAL更活跃，这显然是由于线粒体中5的积累。因此，化合物5可以被认为是一种很有前途的先导化合物，用于测试抗癌和抗菌活性。